Abstract
Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.
Original language | English (US) |
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Article number | 1716 |
Journal | Cancers |
Volume | 16 |
Issue number | 9 |
DOIs | |
State | Published - May 2024 |
Funding
This work was funded by NIH RO1 CA185402 (Li XN), NIH/NCI Pediatric Preclinical Testing Consortium UO1 (1U01CA199288) (Li XN), NIH/NCI Patient-Derived Models of Cancer (PDMC) (UO1 1-U01-CA217613-01A1) (Li XN), NIH/NCI Pediatric Preclinical In Vivo Testing Program (PIVOT) (2UO1 CA199288-06) (Li XN), the Cancer Prevention & Research Institute of Texas (CPRIT) RP150032 and RP-170169 (Li XN), Cure Starts Now Foundation (Li XN), Golfers against Cancer (Li XN), CDMRP DOD PRCRP CA100735 (Li XN), the Childhood Brain Tumor Foundation (Li XN), National Brain Tumor Foundation (LI XN), and St. Baldrick\u2019s Foundation (Grant 2532341503, Su JM).
Keywords
- brain tumor
- cancer
- orthotopic xenograft model
ASJC Scopus subject areas
- Oncology
- Cancer Research